Multiple system atrophy (MSA) is a rare, progressive and ultimately fatal neurodegenerative disease with no known cause and no available disease modifying treatment. Known previously by various names ...including Shy-Drager Syndrome, olivopontocerebellar atrophy (OPCA) and striatonigral degeneration, MSA can be classified simultaneously as a movement disorder, an autonomic disorder, a cerebellar ataxia and an atypical parkinsonian disorder.
Despite scholarly attempts to better describe the disease, awareness among medical practitioners about multiple system atrophy as a diagnostic possibility has been slow to catch on. As a result, patients often go undiagnosed for many years or are largely misdiagnosed as Parkinson's disease. The non-homogeneous clinical presentation of MSA and years of confusing nomenclature have all contributed to a lack of awareness of the disease among healthcare professionals as well as the public. This lack of awareness has amplified the unmet needs of MSA patients and other stakeholders.
Since the 1980s there has been a growing advocacy effort directed at this rare disease from advocacy groups, grassroots supporters, healthcare professionals and research networks. These stakeholders are beginning to unite their efforts and attack the disease from a global perspective in the hopes of improving outcomes for MSA patients in the future.
•Multiple system atrophy (MSA) is a rare, progressive neurodegenerative disease with no available disease modifying treatment.•Awareness by medical practitioners about multiple system atrophy as a diagnostic possibility is severely lacking.•Lack of awareness of the disease has amplified the unmet needs of multiple system atrophy patients and other stakeholders.•Since the 1980’s a growing movement to highlight the plight of those affected by multiple system atrophy has emerged.•Stakeholders are uniting to attack MSA from a global perspective in the hopes of improving outcomes for future patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, ...biological relationship to Parkinson’s disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal “n-of-few” clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (
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eurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a combination of autonomic failure, cerebellar ataxia, and parkinsonism. Laryngeal stridor is an additional feature for ...MSA diagnosis, showing a high diagnostic positive predictive value, and its early occurrence might contribute to shorten survival. A consensus definition of stridor in MSA is lacking, and disagreement persists about its diagnosis, prognosis, and treatment. An International Consensus Conference among experts with methodological support was convened in Bologna in 2017 to define stridor in MSA and to reach consensus statements for the diagnosis, prognosis, and treatment. Stridor was defined as a strained, high-pitched, harsh respiratory sound, mainly inspiratory, occurring only during sleep or during both sleep and wakefulness, and caused by laryngeal dysfunction leading to narrowing of the rima glottidis. According to the consensus, stridor may be recognized clinically by the physician if present at the time of examination, with the help of a witness, or by listening to an audio recording. Laryngoscopy is suggested to exclude mechanical lesions or functional vocal cord abnormalities related to different neurologic conditions. If the suspicion of stridor needs confirmation, drug-induced sleep endoscopy or video polysomnography may be useful. The impact of stridor on survival and quality of life remains uncertain. Continuous positive airway pressure and tracheostomy are both suggested as symptomatic treatment of stridor, but whether they improve survival is uncertain. Several research gaps emerged involving diagnosis, prognosis, and treatment. Unmet needs for research were identified.
Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a combination of autonomic failure plus cerebellar syndrome and/or parkinsonism. Dysphagia is a frequent and disabling ...symptom in MSA and its occurrence within 5 years of motor onset is an additional diagnostic feature. Dysphagia can lead to aspiration pneumonia, a recognized cause of death in MSA. Guidelines for diagnosis and management of dysphagia in MSA are lacking. An International Consensus Conference among experts with methodological support was convened in Bologna to reach consensus statements for the diagnosis, prognosis, and treatment of dysphagia in MSA. Abnormalities of the oral and pharyngeal phases of swallowing, esophageal dysfunction and aspiration occur in MSA and worsen as the disease progresses. According to the consensus, dysphagia should be investigated through available screening questionnaires and clinical and instrumental assessment (videofluoroscopic study or fiberoptic endoscopic evaluation of swallowing and manometry) at the time of MSA diagnosis and periodically thereafter. There is evidence that dysphagia is associated with poor survival in MSA, however effective treatments for dysphagia are lacking. Compensatory strategies like diet modification, swallowing maneuvers and head postures should be applied and botulinum toxin injection may be effective in specific conditions. Percutaneous endoscopic gastrostomy may be performed when there is a severe risk of malnutrition and pulmonary complications, but its impact on survival is undetermined. Several research gaps and unmet needs for research involving diagnosis, prognosis, and treatment were identified.
•Dysphagia is a frequent and disabling symptom in MSA.•Dysphagia can lead to aspiration pneumonia, a cause of death in MSA.•Consensus statements for diagnosis, prognosis, treatment of dysphagia are supplied.•Unmet needs for research on dysphagia in MSA are also identified.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Young people don't necessarily care about such things as not falling over and breaking their leg; that can sound hilarious. But they do care about not getting the text message from their friends ...about going out on Friday night. They do mind being excluded from the group because they've been such an idiot over the past few weeks. If people have been drinking excessively, they can't get into pubs and it shortens their night out. In the end, that has an impact. So Diageo take this idea of the fear of 'social erosion' and make it the heart of our communications. But why should a brand like Diageo be so concerned with social issues like excess drinking? From a commercial point of view, it's important for business sustainability. It's not a corporate responsibility issue, however. They market the responsible drinking message as they would any of their other brands. By giving it equal weight with their other products, such as Gordon's or Bell's, it is not seen as a legal add-on.
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CEKLJ, IZUM, KILJ, NUK, PILJ, SAZU, UL, UM, UPUK
In the present study, we compared changes in risk factors for cardiovascular disease (CVD) before and after natural menopause (NM), hysterectomy with at least 1 ovary conserved (HOC), or hysterectomy ...with bilateral oophorectomy (HBSO). Data were obtained from women 18-30 years of age who were enrolled in the Coronary Artery Risk Development in Young Adults Study (1985-2011). Piecewise linear mixed models were used to examine changes in CVD risk factors from baseline to the index visit (the first visit after the date of NM or hysterectomy) and after index visit until the end of follow-up. During 25 years of follow-up, 1,045 women reached menopause (for NM, n = 588; for HOC, n = 304; and for HBSO, n = 153). At baseline, women with either type of hysterectomy had less favorable values for CVD risk factors. When comparing the annual rates of change of all CVD risk factors from baseline until the index visit to those from the index visit to the end of follow-up, we saw a small increase in rate of change for high-density lipoprotein cholesterol (β = 0.28 mg/dL; P = 0.002) and a decrease for triglycerides (β =-0.006 mg/dL; P = 0.027) for all groups. Hysterectomy was not associated with risk factors for CVD after accounting for baseline values. However, antecedent young-adult levels of CVD risk factors were strong predictors of levels of postmenopausal risk factors.
Background: Women with GDM have seven times higher risk of T2D compared to women with normoglycaemic pregnancies, with black women having the highest risk. Immigrants are a growing share of the U.S. ...population, with approximately 9% of the black population and 34% of Hispanic population being foreign-born. Due to differences in acculturation and assimilation, foreign-born U.S. women experience different pregnancy-related outcomes and subsequent chronic disease development, depending on their race/ethnicity.
Objective: To examine the association between nativity and T2D diagnosis following a prior GDM pregnancy and whether this association differs by racial/ethnic group.
Methods: We conducted a cross-sectional analysis of data from the 2007-2014 National Health and Nutrition Examination Survey, a nationally representative survey of non-institutionalized Americans. The analytic population included women with at least one prior GDM pregnancy. Logistic regression (OR, 95% CI) was used to examine the association.
Results: Our final sample included 433 women. The population was predominantly non-Hispanic white (62%), followed by Hispanic (18%) and black (12%). T2D was found in 29% of the population. After controlling for confounders, foreign-born black women had 0.14 (0.02-0.82) times the odds of developing T2D post GDM compared to black U.S. born women. Nativity was not significantly associated with cumulative incidence of T2D among Hispanics (1.45, 0.48-4.41) or non-Hispanic whites (1.53, 0.04,-6.07).
Conclusion: We found differential effects of nativity across racial/ethnic groups consistent with prior literature. Among black women, being foreign-born significantly decreases the odds of developing T2D following a GDM pregnancy but not among other groups. This observed effect may be due to U.S. born black women experiencing higher levels of racialized and gendered stress, both associated with higher levels of inflammation that can lead to higher risk of T2D.
Disclosure
B. Butler: None. P. Salsberry: None. J.K. Bower: None.
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